Droxidopa as an effective treatment for refractory neurogenic orthostatic hypotension and reflex bradycardia in amyloid light-chain amyloidosis: a case report.

BACKGROUND: Droxidopa is an oral treatment for the stepwise treatment of neurogenic orthostatic hypotension from autonomic dysfunction. It has been shown to be useful predominantly with neurogenic orthostatic hypotension secondary to Parkinson's disease, but only a few cases have documented its usefulness in patients with neurogenic orthostatic hypotension due to amyloidosis, which is often severe and refractory. In addition, only one source in the literature reports the concomitant use of midodrine and droxidopa for such patients. Finally, we argue that droxidopa seems to have a protective effect against episodes of reflex bradycardia, which is not previously reported. CASE PRESENTATION: A 64-year-old white man was admitted for 1 year of worsening syncopal episodes, diarrhea, failure to thrive, heart failure, and neuropathy. Medical emergencies were called five times on the overhead hospital intercom over a 4-day period in the beginning of his admission due to severe hypotension and bradycardia. He was eventually diagnosed as having amyloid light-chain amyloidosis and myeloma. After starting droxidopa, both his systolic blood pressure and reflex bradycardia improved, and no more medical emergency events were called during the remaining 30 days of admission. He felt much better subjectively and was able to sit upright and engage in physical therapy. CONCLUSIONS: We show that droxidopa is effective when used with midodrine to treat refractory neurogenic orthostatic hypotension in patients with amyloidosis. There are very few cases reporting the use of droxidopa in amyloidosis, with only one study that uses droxidopa and midodrine concomitantly. In addition, our patient's reflex bradycardia improved drastically after starting droxidopa, which we believe is mediated by increased systemic norepinephrine. There were no side effects to droxidopa, and the benefits lasted well beyond the reported duration of 1-2 weeks that was noted to be a limitation in some studies.

Prolonged reflex bradycardia after occlusion of patent ductus arteriosus with an Amplatz canine duct occluder in a dog

A 9-month-old intact male Maltese dog (1.52 kg) was diagnosed with a patent ductus arteriosus (PDA). Transcatheter occlusion of the PDA was performed by using the Amplatz canine duct occluder (ACDO). After occlusion, reflex bradycardia occurred and lasted for at least 15 h with normal systolic arterial pressure and slightly increased diastolic arterial pressure. The bradycardia slowly resolved, and the heart rate was normal in re-examinations after 7 and 30 days. This is the first case of reflex bradycardia after ACDO implantation, in which the bradycardia continued for a long time, even after recovery from anesthesia.

Central 5-HT2A receptors modulate the vagal bradycardia in response to activation of the von Bezold-Jarisch reflex in anesthetized rats

Activation of 5-hydroxytryptamine (5-HT) 5-HT1A, 5-HT2C, 5-HT3, and 5-HT7 receptors modulates the excitability of cardiac vagal motoneurones, but the precise role of 5-HT2A/2B receptors in these phenomena is unclear. We report here the effects of intracisternal (ic) administration of selective 5-HT2A/2B antagonists on the vagal bradycardia elicited by activation of the von Bezold-Jarisch reflex with phenylbiguanide. The experiments were performed on urethane-anesthetized male Wistar rats (250-270 g, N = 7-9 per group). The animals were placed in a stereotaxic frame and their atlanto-occipital membrane was exposed to allow ic injections. The rats received atenolol (1 mg/kg, iv) to block the sympathetic component of the reflex bradycardia; 20-min later, the cardiopulmonary reflex was induced with phenylbiguanide (15 µg/kg, iv) injected at 15-min intervals until 3 similar bradycardias were obtained. Ten minutes after the last pre-drug bradycardia, R-96544 (a 5-HT2A antagonist; 0.1 µmol/kg), SB-204741 (a 5-HT2B antagonist; 0.1 µmol/kg) or vehicle was injected ic. The subsequent iv injections of phenylbiguanide were administered 5, 20, 35, and 50 min after the ic injection. The selective 5-HT2A receptor antagonism attenuated the vagal bradycardia and hypotension, with maximal effect at 35 min after the antagonist (pre-drug = -200 ± 11 bpm and -42 ± 3 mmHg; at 35 min = -84 ± 10 bpm and -33 ± 2 mmHg; P < 0.05). Neither the 5-HT2B receptor antagonists nor the vehicle changed the reflex. These data suggest that central 5-HT2A receptors modulate the central pathways of the parasympathetic component of the von Bezold-Jarisch reflex.